Worldwide, cervical cancer is the second most common form of female cancer with incidence of over 500,000 new cases and 300,000 deaths each year. However, if detected early, cervical cancer precursors can be treated effectively. Research worldwide has clearly shown that virtually all cervical cancer is caused by human papillomavirus (HPV) (1-5). In addition, carcinogenic HPV also causes about 200,000 cases of cancer in other sites such as oropharynx, anus, oral cavity, larynx, vulva, and penis worldwide annually. Women persistently infected with certain carcinogenic types are at increased risk of developing severe dysplasia leading to cervical cancer. Cervical cancer prevention programs in both developed and developing nations generally have relied on cytological testing using the Papanicolaou (Pap) smear test (6). Pap smears require that a health care provider obtain a sample of cells from the uterine cervix of each woman screened. Trained technicians then examine the specimen for cellular changes (dysplasia) known to precede the development of cervical cancer. Such screening programs can be expensive, prone to error, and less sensitive (7-10). The direct detection of HPV in cervical specimens offers an alternative or complement to population-based cytological screening. Recent studies have demonstrated that molecular HPV test results are more sensitive than Pap smears in detecting cervical cancer. There are over 100 different HPV types of which only 15 are known as high risk, those typically associated with cervical cancer, whereas three others are known as probable high risk because of their low prevalence rate. Recent studies show that not all HPV types are equally prevalent or carcinogenic (11). For example, the odd ratio or the likelihood of developing cervical cancer with the presence of HPV16 is 434× greater than without HPV16, whereas it is 45× greater in the presence of HPV45 than without HPV45.
Human Papilloma Viruses are small, double-stranded DNA viruses that infect mucosal and cutaneous epithelia through tiny cuts and abrasions that expose cells of the basal layers. Benign diseases such as hand warts, laryngeal warts, verrucas and numerous other skin lesions can be attributed to infection by one of the 100-plus members of the family of HPV. The individual virus types are defined by DNA sequence homology, and the resulting phylogenetic trees (12-13) can also be related to the pathologies induced by specific types.
The cloning of HPV genomes into bacterial plasmid vectors in the early 1980s (14) later led the realization that HPV infection was linked to cervical cancer. The consequent surge in research activity indicated that over 99% of cervical tumors contain HPV DNA, around 65% being positive for one of the two commonest high-risk types, HPV 16 and 18. DNA sequence determination and classification led to the identification of HPV types such as 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73 and 82 were termed ‘high risk for cancer induction’, and 26, 53, and 66 were termed ‘probably high risk’, while twelve others (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81) were grouped together as ‘low risk’.
Prompt and accurate diagnosis is the key to effective disease management and contributes significantly to positive outcomes in many aggressive and life threatening illnesses. Early detection of specific etiologic agents will improve patient management and critically reduce morbidity, mortality of patients, and costs. Modern diagnostic possibilities such as real time polymerase chain reaction (PCR) and genetic chips that identify the cause of the disease prior to the symptoms appearing can help to set new standards in early detection and treatment.
The traditional methods for HPV detection, such as morphological and immunological methods, show low sensitivity and specificity, and do not detect each specific HPV genotype present. However, these methods have many disadvantages, such as requiring a great deal of time and labor to perform the test, the risk of using radioactive isotope, low specificity, high false positive/negative rate, and/or inconvenience in the processes of sample management. Therefore, there is a need in the field for a test with greater specificity that can be done with greater speed.